Hydrogen inhalation provides significant cardioprotective effects in diabetic cardiomyopathy by inhibiting pyroptosis through the AMPK/mTOR/NLRP3 pathway and reducing fibrosis via TGF-β1/Smad inhibition. Co-administration of hydrogen with metformin demonstrates superior therapeutic efficacy compared to metformin monotherapy, offering a promising novel combination strategy for managing diabetic cardiac complications with reduced drug dosing requirements.
Plain-Language Summary
This study tested whether hydrogen gas could help protect the heart in mice with diabetes-related heart damage (a condition called diabetic cardiomyopathy). Researchers found that hydrogen gas improved heart function and structure in diabetic mice, and that combining hydrogen with metformin (a common diabetes medication) worked better than metformin alone. The study suggests hydrogen may work by reducing harmful cell death processes and scar tissue formation in the heart.
Abstract
Hydrogen is a novel medical gas with several properties, including anti-oxidative, anti-inflammatory, anti-apoptotic, anti-allergic, and energy metabolism stimulating properties. Hydrogen therapy has been proven effective in the treatment of myocardial ischemia, myocardial infarction, and ischemia-reperfusion injury. Diabetic cardiomyopathy (DCM) is a serious cardiovascular complication of long-term chronic diabetes that is linked to increased heart failure and arrhythmia morbidity. The effect of hydrogen on the pathogenesis of DCM is yet to be determined. Metformin is a well-known pharmacological agent for the treatment of diabetes; however, the application of large doses of the drug is limited by its side effects. Therefore, this highlights the importance of developing novel therapies against DCM. In this regard, we investigated the effect of hydrogen on DCM and the mechanisms that underlie it. Furthermore, we also assessed the efficacy of co-administration of metformin and hydrogen. In this study, we found that hydrogen improved cardiac dysfunction and abnormal morphological structure in streptozotocin-induced diabetic mice. As a mechanism, it was confirmed that hydrogen mediated its action by reducing pyroptosis via inhibition of the AMPK/mTOR/NLRP3 signaling pathway and ameliorating fibrosis via inhibition of the TGF-β1/Smad signaling pathway. Furthermore, our findings suggested that co-administration of hydrogen and metformin shows potent protective effects, as evidenced by increased survival rates, reduced fasting blood glucose, and decreased cell injury when compared to a single application of metformin. In conclusion, our study demonstrated that hydrogen inhalation attenuates DCM by reducing pyroptosis and fibrosis and that hydrogen can be combined with metformin to exhibit a more potent cardioprotective effect in DCM.
